Injectable Nanoparticles for Soft Tissue Recovery and Strength Enhancement

In the U.S., there are over 32 million traumatic and repetitive motion injuries to ligaments and tendons each year, costing $30 billion. Sprains (ligament injuries) and strains (tendon and muscle injuries) account for 5.7 million visits to emergency rooms. In 2002, approximately 200,000 Americans required ligament reconstructive surgery costing over $5 billion. Joint dislocations are more frequent for those with connective tissue disorders like Ehlers-Danlos Syndrome (EDS), a group of genetic connective tissue disorders that cause defective collagen production. Patients with EDS frequently experience joint dislocations from unstable joints that can be painful and debilitating. As a solution to sprains, strains, and joint dislocations, this project proposes an injectable therapy to return the tissue to its normal length and strengthen it using a natural, bond-forming agent to prevent reinjury/future injury. This project will also create research opportunities for underrepresented and first-generation undergraduate students during the summers and throughout the school year. It will also create opportunities for underrepresented students in underserved elementary schools to learn about biomedical engineering through presentations and hands-on experiments. The overall goal of this project is to investigate the combination of a thermosensitive polymer and crosslinking agent to quickly stabilize joints by restoring strength and original length to damaged tendons and ligaments. This will be accomplished by studying the contraction of poly(N-isopropylacrylamide) (pNIPAm) and the effectiveness of epigallocatechin-3-gallate (EGCG) crosslinking in vivo. The research approach is divided into three areas. First, collagen-binding contractile nanoparticles will be created and evaluated. This step will alter nanoparticle composition and pNIPAm concentration to maximize contraction and bind to collagen fibers. Second, the EGCG release and its effect on cell behavior and tissue strength will be evaluated. The concentrations of EGCG that create maximum collagen crosslinking, while remaining nontoxic to surrounding cells will be discovered. Third, the contractile and tissue strengthening ability of the nanoparticles in vivo will be evaluated. Nanoparticles with compositions based on the earlier two tasks will be injected into a damaged tendon model. After injection, they will be evaluated for their effect on gait, length after injection, and strength. If successful, this innovative, therapy would benefit millions of people by increasing strength, improving wound healing, and quickly stabilizing damaged joints. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.